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Developmental Biology - Botanical Medicines|
How Folk Medicines Affect Hypertension
"We found KCNQ5 activation to be a unifying molecular mechanism shared by a diverse range of botanical hypotensive folk medicines. Lavandula angustifolia, commonly called lavender, was among those we studied.
Botanical folk medicines have been used throughout human history to treat common disorders such as hypertension, often with unknown underlying mechanisms. Here, we discovered that hypotensive folk medicines from a genetically diverse range of plant species each selectively activated the vascular-expressed KCNQ5 potassium channel, a feature lacking in the modern synthetic pharmacopeia, whereas nonhypotensive plant extracts did not. Analyzing constituents of the hypotensive Sophora flavescens root, we found that the quinolizidine alkaloid aloperine is a KCNQ-dependent vasorelaxant that potently and isoform-selectively activates KCNQ5 by binding near the foot of the channel voltage sensor. Our findings reveal that KCNQ5-selective activation is a defining molecular mechanistic signature of genetically diverse traditional botanical hypotensives, transcending plant genus and human cultural boundaries. Discovery of botanical KCNQ5-selective potassium channel openers may enable future targeted therapies for diseases including hypertension and KCNQ5 loss-of-function encephalopathy.
Botanical folk medicines have been used by diverse human populations and cultures for several millennia. Many are still in use today, but the underlying molecular mechanisms often remain elusive. Here we report the discovery of a molecular mechanism linking diverse plant extracts used traditionally to lower blood pressure (hypotensives). All of the hypotensive plants tested activated the KCNQ5 vascular-expressed potassium channel, whereas nonhypotensives did not. For one hypotensive plant, we describe discovery of the active small molecule (aloperine) and demonstrate that it KCNQ-dependently relaxes blood vessels. The discovery opens up a new source of potential therapeutic drugs and explains the mechanism behind folk hypotensive medicines used by diverse populations for thousands of years.
Rían W. Manville, Jennifer van der Horst, Kaitlyn E. Redford, Benjamin B. Katz, Thomas A. Jepps and Geoffrey W. Abbott.
Acknowledgements This study was supported by the National Institutes of Health, National Institute of General Medical Sciences and the National Institute of Neurological Disorders and Stroke. Also involved in the study were UCI's Rían Manville, PhD, PhD student Kaitlyn Redford and Benjamin Katz, PhD, and from the University of Copenhagen, Denmark, PhD student Jennifer van der Horst and Thomas Jepps, PhD.
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Lavender (Lavandula angustifolia), a plant widely used in herbal teas, essential oils, soaps and
lotions, was discovered to be among the most efficacious KCNQ5 potassium channel activators.
CREDIT Bo Abbott